Tectoridin alleviates caerulein-induced severe acute pancreatitis by targeting ERK2 to promote macrophage M2 polarization.

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.

Effective Synthesis of High-Integrity mRNA Using In Vitro Transcription.

mRNA vaccines are entering a period of rapid development. However, their synthesis is still plagued by challenges related to mRNA impurities and fragments (incomplete mRNA). Most impurities of mRNA products transcribed in vitro are mRNA fragments. Only full-length mRNA transcripts containing both a 5'-cap and a 3'-poly(A) structure are viable for in vivo expression. Therefore, RNA fragments are the primary product-related impurities that significantly hinder mRNA efficacy and must be effectively controlled; these species are believed to originate from either mRNA hydrolysis or premature transcriptional termination. In the manufacturing of commercial mRNA vaccines, T7 RNA polymerase-catalyzed in vitro transcription (IVT) synthesis is a well-established method for synthesizing long RNA transcripts. This study identified a pivotal domain on the T7 RNA polymerase that is associated with erroneous mRNA release. By leveraging the advantageous properties of a T7 RNA polymerase mutant and precisely optimized IVT process parameters, we successfully achieved an mRNA integrity exceeding 91%, thereby further unlocking the immense potential of mRNA therapeutics.

Size-Independent Reconfigurable Logic Gate with Bismuth Oxide Based Photoelectrochemical Device.

XOR gate, an important building block in computational circuits, is often constructed by combining other basic logic gates, and the hybridity inevitably leads to its complexity. A photoelectrochemical device could realize XOR function based on the current change of the photoelectrode; however, such signal is highly sensitive to photoelectrode size and therefore requires precise manufacturing at a high cost. Herein we developed a novel XOR gate based on the light-induced open-circuit potential (OCP) of the Bi2O3 photoelectrode. Surprisingly, the OCP of Bi2O3 does not increase with light intensity according to the traditional logarithmic relationship. Instead, an unusual decrease in OCP is observed at high light intensity, which is attributed to the dramatic light-induced increase in surface states that can be easily regulated by varying the oxygen partial pressure during reactive magnetron sputtering. Based on such a nonmonotonic variation of OCP, a facile Bi2O3-based gate is designed to realize the XOR function. Unlike the commonly used current signal, OCP is size independent, and therefore, the Bi2O3-based gate does not require high manufacturing accuracy. Moreover, in addition to XOR, the Bi2O3-based PEC gate also demonstrates great versatility in realizing other logic functions including AND, OR, NOT, NIH, NAND, and NOR. The strategy of modulating and applying nonmonotonic OCP signal opens a new avenue for designing size-independent reconfigurable logic gates at low manufacturing cost.

A Sensitive Concentration- and Polarity-Dependent Pyrene-Derived Vibrationally Resolved Fluorescence Probe for The Polymer Interdiffusion Study.

The vibrationally resolved pyrene fluorescence probe method is once popular but now languished, because the vibrationally resolved patterns of pyrene with limited sensitivity and concentration independence have not been updated for over 50 years. During investigation on the polymer interdiffusion of a latex film, it is found that a pyrene acylhydrazone whose vibrationally resolved fluorescence pattern contradictory to those reported in pyrene and most pyrene derivatives. The pyrene acylhydrazone has sensitive concentration- and polarity-dependent fluorescence spectra (the sensitivity on polarity is at most 26 times higher than the old vibrationally resolved patterns), and the sensitivity well remains when it is copolymerized in a polymer. The vibrationally resolved spectrum of this pyrene acylhydrazone is a powerful fluorescence probe, which would be as useful as the pyrene excimer probe nowadays popular.

Protective effects of Typhonii Rhizoma in rheumatoid arthritis rats revealed by integrated metabolomics and network pharmacology.

Rheumatoid arthritis (RA) is an autoimmune disease with a 0.5% prevalence worldwide. Inflammation, periosteal proliferation and joint destruction are the main clinical symptoms of RA. Typhonii Rhizoma (TR) is the dry tuber of the Araceae plant Typhonium giganteum Engl, and possesses many uses such as dispelling obstructive wind-phlegm and relieving pain. It is used for the clinical treatment of arthromyodynia and RA. However, the mechanism of action remains unclear. In this study, we first evaluated the effects of TR in type II collagen-induced RA model rats. Secondly, in serum metabolomics, TR could ameliorate 11 potential metabolites in RA model rats and reversed RA through pentose and glucuronate interconversions, sphingolipid metabolism, glycerophospholipid metabolism and tryptophan metabolism. To further explore the mechanisms of TR, 40 chemical constituents were used to establish a component-target interaction network. Some key genes were verified by in vitro pharmacological tests by integrating the results from the network pharmacology and metabolomics. The verification results showed that the mechanisms of TR against RA may be related to the inhibition of the production of inflammatory cytokines and the expression and function of HIF1-α. This study serves as a theoretical basis for the treatment of RA with TR.

Enhanced Activity of Enzyme Immobilized on Hydrophobic ZIF-8 Modified by Ni2+ Ions.

The development of efficient enzyme immobilization to promote their recyclability and activity is highly desirable. Zeolitic imidazolate framework-8 (ZIF-8) has been proved to be an effective platform for enzyme immobilization due to its easy preparation and biocompatibility. However, the intrinsic hydrophobic characteristic hinders its further development in this filed. Herein, a facile synthesis approach was developed to immobilize pepsin (PEP) on the ZIF-8 carrier by using Ni2+ ions as anchor (ZIF-8@PEP-Ni). By contrast, the direct coating of PEP on the surface of ZIF-8 (ZIF-8@PEP) generated significant conformational changes. Electrochemical oxygen evolution reaction (OER) was employed to study the catalytic activity of immobilized PEP. The ZIF-8@PEP-Ni composite attains remarkable OER performance with an ultralow overpotential of only 127 mV at 10 mA cm-2 , which is much lower than the 690 and 919 mV overpotential values of ZIF-8@PEP and PEP, respectively.

In situ hybridization assay for circular RNA visualization based on padlock probe and rolling circle amplification.

Circular RNAs (circRNAs) are a class of noncoding RNAs generated by a specific type of RNA alternative splicing called backsplicing through various mechanisms. Recently, thousands of circRNAs have been identified by high-throughput RNA sequencing technologies and bioinformatics analysis. However, the functions of the majority have not been fully elucidated yet. Different tools, such as in situ hybridization, can help visualize the spatial temporal distribution of circRNA molecules, thus assisting the understanding of their biological and physiological functions. Here, we present a simple and straightforward method based on padlock probe hybridization and rolling circle amplification (RCA) for in situ detection of circRNAs. We compared our method with the commercially available BaseScope assay for the detection of Cdr1as in the mouse brain tissue. The result showed that the two methods have achieved comparable detection efficiency, thus demonstrating our padlock probe assay as an alternative yet simple circRNA in situ detection method for the research community.

Fabrication of Temperature- and Alcohol-Responsive Photonic Crystal Hydrogel and Its Application for Sustained Drug Release.

Herein, crack-free photonic crystal templates with enhanced color contrast were first demonstrated by the coassembly of polystyrene (PS) microspheres and graphene oxide (GO). Then, photonic crystal hydrogels (PCHs) with quick responses to temperature and alcohol solution concentration changes were fabricated by photopolymerization of monomers in the gaps of the self-assembled colloidal crystal templates. The structural color of the PCHs changed from yellow to blue within 120 s as the temperature rose from 25 to 40 °C, whereas upon a decrease in temperature from 40 to 25 °C, the structural color changed from blue to yellow. The structural color of the PCHs also shows an obvious response with the concentration of alcohol solution ranging from 40 to 100 wt %. The quick responses of the PCHs' structural color to changes in temperature and alcohol solution concentration are attributed to the temperature sensitivity of poly(N-isopropylacrylamide) and preferential adsorption and swelling of the alcohol solution for the polymer chains. Furthermore, moxifloxacin (Mox) was loaded into PCHs by hydrogel swelling and exhibited sustained released by increasing the temperature. The sustained release process was facilely monitored by observing the corresponding color changes in real time. The rapid and visible response offers the fabricated PCHs great potential application prospects in the semiquantitative analysis of alcohol concentration and intelligent drug delivery.

L-Proline-methyl ester derivative-modulated synthesis of gold nanoclusters with promoted peroxidase-mimic activity for monitoring of ofloxacin.

Gold nanoclusters (AuNCs), stabilized and functionalized by organic ligands, have served as new generation materials for applications in nanocatalysis. To further expand and regulate the catalytic function of AuNCs, the exploration of surface interactions and modulated-ligand properties is highly desirable. This study presents the fabrication of four kinds of AuNCs using L-proline-methyl ester derivatives as ligands. Among these AuNCs nanocatalysts, the highest peroxidase-mimic catalytic activity in an oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB) with hydrogen peroxide is observed when using L-proline-methyl ester capped AuNCs (POMe@AuNCs) as the nanozymes. Notably, the addition of ofloxacin in the oxidation system yields more reactive oxygen species, resulting in a significant increase in catalytic capability. A colourimetric sensing strategy is developed for the highly selective and sensitive measurement of ofloxacin. The UV-vis absorption of oxTMB at 650 nm exhibits a good linear relationship with the ofloxacin amount, ranging from 0.6 µM to 12.0 µM (R2 = 0.998), and the detection limit is 0.2 µM. The protocol further displays its potential application in monitoring rat serum ofloxacin variation in a drug-metabolic-process. This study not only demonstrates a unique strategy for the ligand-modulated synthesis of AuNCs, but also guides future detection of drugs that can enhance the catalytic capability of AuNCs.

Mussel-inspired hydrogels as tough, self-adhesive and conductive bioelectronics: a review.

To overcome the wearable sensor's defects and achieve the goal of robust mechanical properties, long-term adhesion, sensitive electrical conductivity, the multifunctional hydrogels were inspired by various mussels on the base of catechol and its analogues. In this review, we review the strategies for improving the mechanical strength, adhesion, conductivity and antibacterial properties of mussel-inspired hydrogels as bioelectronics. Double network structures, nanocomposites, supramolecular block polymers and other strategies were utilized for achieving tough hydrogels to prevent tensile fractures under high deformation. Many mussel-inspired chemistries were incorporated for constructing skin-attachable hydrogel strain sensors and some strategies for controlling the oxidation of catechol were employed to achieve long-term adhesion. In addition, electrolytes, conductive fillers, conductive polymers and their relevant hydrophilic modifications were introduced for fabricating the conductive hydrogel bioelectronics to enhance the conductivity properties. Finally, the challenges and outlooks in this promising field are featured from the perspective of materials chemistry.

Boosting the peroxidase-like activity of gold nanoclusters for the colorimetric detection of oxytetracycline in rat serum.

Gold nanoclusters (AuNCs)-based nanozymes have been studied widely as they provide unrivaled advantages in terms of preferable enzyme-like activities, high stability, and good biocompatibility. Although the enzyme-like catalytic activity of AuNCs has been the object of extensive investigation, understanding how charges or reactive oxygen species on the surfaces of AuNCs can enhance their catalytic performance in the colorimetric sensing of drugs by regulating the catalytic activity of AuNCs is still a big challenge. Herein, l-tryptophanonitrile (LTN)-protected AuNCs (LTN@AuNCs) were prepared, and their nanozyme activity was investigated in the catalytic oxidation process of the peroxidase substrate, namely 3,3',5,5'-tetramethylbenzidine, in the prescence of hydrogen peroxide. Oxytetracycline induced the aggregation of LTN@AuNCs due to the electrostatic interaction between the positively charged LTN@AuNCs and the negatively charged drug. Importantly, the aggregated LTN@AuNCs produced more reactive oxygen species and significantly boosted their peroxidase-like activity. Subsequently, a colorimetric method for highly specific and sensitive detection of oxytetracycline was establised. The ultraviolet-visible absorbance at a wavelength of 650 nm of the aggregated-LTN@AuNCs exhibited a good linear relationship with oxytetracycline in a range of 0.5-15.0 µM (R2 = 0.994). The limit of detection was 0.3 µM. After oxytetracycline was abdominally injected in rats, the metabolic process of the drug in serums was further investigated by using the proposed sensing protocol. The improvable catalytic activity capability of the AuNCs-based nanozymes discloses its great potential in real bio-applications.

Angle-Dependent Polarized Emission and Photoelectron Performance of Dye-Encapsulated Metal-Organic Framework.

Molecule-based crystalline materials with angle-dependent polarized emission have attracted considerable attention owing to their extensive applications in displays and anticounterfeiting. Herein, one anionic metal-organic framework (MOF) {[Zn2.5(µ3-OH)(NDC)2(HNDC)](HPIM)}n was constructed on the basis of an excellent photoactive ligand naphthalene-1,4-dicarboxylic acid (H2NDC). The protonated 2-propylimidazole (HPIM) guests residing in the nanochannels of MOF can be exchanged by a D-π-A cationic dye. The resulted host-guest system shows a rare example of ratiometric fluorescent polarizations and highly enhanced photoelectron performance in comparison with the pristine MOF.

Dual-stimuli-responsive porous polymer enzyme reactor for tuning enzymolysis efficiency.

A strategy for preparing a dual-stimuli-responsive porous polymer membrane enzyme reactor (D-PPMER) is described, consisting of poly (styrene-maleic anhydride-N-isopropylacrylamide-acrylate-3',3'-dimethyl-6-nitro-spiro[2H-1-benzopyran-2,2'-indoline]-1'-esterspiropyran ester) [P(S-M-N-SP)] and D-amino acid oxidase. Tunable control via "on/off" 365 nm UV light irradiation and temperature variation was used to change the membrane surface configuration and adjust the enzymolysis efficiency of the D-PPMER. A chiral capillary electrophoresis technique was developed for evaluation of the enzymatic efficiency of D-PPMER with a Zn(II)-dipeptide complex as the chiral selector and D,L-serine as the substrate. Interestingly, the enzymatic kinetic reaction rate of D-PPMER under UV irradiation at 36 °C (9.2 × 10-2 mM·min-1) was 3.2-fold greater than that of the free enzyme (2.9 × 10-2 mM·min-1). This was because upon UV irradiation at high temperature, the P(SP) and P(N) moieties altered from a "stretched" to a "curled" state to encapsulate the enzyme in smaller cavities. The confinement effect of the cavities further improved the enzymatic efficiency of the D-PPMER. This protocol highlights the outstanding potential of smart polymers, enables tunable control over the kinetic rates of stimuli-responsive enzyme reactors, and establishes a platform for adjusting enzymolysis efficiency using two different stimuli.

Anisotropic Hexagonal Particles Induced by the Double-Solvent Swelling Method.

Nonspherical anisotropic particles, as basic building blocks, have been catching much attention in recent decades. However, it is still a challenge to produce nonspherical particles by traditional approaches. Here, we reported a facile method to fabricate hexagonal particles via the double-solvent swelling method. When the crystal arrays were immersed in the double-solvent system of N,N-dimethylformamide (DMF) and tetraethyl orthosilicate (TEOS), the particles were swollen and squeezed into hexagonal particles. The concave size of hexagonal particles was controlled by tuning the mass ratio of the solvent and the swelling time. In addition, the particles with novel morphology were also prepared by swelling the arrays with a distinct lattice structure. The monodispersed particle possesses a well-defined hexagonal morphology and the liquid crystal phenomenon, which has promising applications in the fields of photonics, optical devices, and toners.

Non-Close-Packed Particle Arrays Based on Anisotropic Red Blood Cell (RBC) like Particles via Stretching Deformation Method.

Non-close-packed (NCP) particle arrays have potential applications in many fields such as photonics and sensors. However, due to thermodynamic stability, it is still a challenge to produce NCP arrays by the traditional approach. Here, we demonstrated a facile method to fabricate hexagonal close-packed (HCP) arrays with different orientations from that of the Janus particles. After that, the HCP arrays can be easily tuned by stretching deformation of polyethylene film. By tuning the stretching elongations, NCP arrays with five Bravais lattice structures were obtained. Besides, to fabricate the complex structure, these arrays were used as templates to assemble binary particle arrays. Such tunable crystal lattice and binary self-assembly crystal can be useful for fabricating more flexible structures and more open systems.

Real-time subtraction-based calibration methods for deformation measurement using structured light techniques.

Calibration of the optical trigonometric relationships in structured light is essential for the accuracy of out-of-plane displacement measurement. A simple calibration mechanism based on real-time image subtraction is proposed. Details of calibrating the height-to-phase ratio of the digital fringe projection method, the relationship between out-of-plane and in-plane displacements of the digital projection-speckle correlation method, and the scale factor of the optical system are described. The calibration methods are applied to the deformation measurement of a clamped Plexiglas plate, which demonstrates the effectiveness of the calibration methods. The real-time subtraction-based calibration methods provide alternatives for calibrating structured light techniques used for out-of-plane displacement measurement.

Self-assembly of anisotropic red blood cell (RBC)-like colloidal particles.

Non-spherical colloidal particles, as basic building blocks, exhibit special capability in constructing novel materials. In this work, red blood cell (RBC)-like, anisotropic particles were synthesized and the self-assembly of the RBC-like particles was then carried out at the air-water interface. Subsequently, multilayer 3D structured colloidal crystals were also fabricated. The as-prepared colloidal crystal film displays beautiful Bragg diffraction, which can be used to construct a photonic crystal. After that, the self-assembly of binary colloidal particles was explored to design well-patterned binary colloidal crystals. This facile self-assembly approach to prepare colloidal crystals may extend to other anisotropic building blocks, providing guidance for the fabrication of more complex and flexible materials.

Uniform distribution of graphene oxide sheets into a poly-vinylidene fluoride nanoparticle matrix through shear-driven aggregation.

A general methodology has been developed for preparing nanocomposites with uniform, random distribution of fillers in polymer matrices, purely based on intense shear-driven aggregation, while avoiding filler aggregation. This procedure is demonstrated for a binary colloid composed of graphene oxide (GO) sheets and poly-vinylidene fluoride (PVDF) nanoparticles (NPs), both negatively charged and stable at rest. On the other hand, the PVDF NPs are shear-active (i.e. aggregation occurs under intensive shear), while the GO sheets are shear-inactive. It is found that when the two suspensions are mixed and the resulting binary colloid is forced to pass through a microchannel (MC) device (at a very high shear rate, G = 1.2 × 10(6) s(-1)), the shear-inactive GO sheets are captured and well distributed inside the PVDF NP clusters or gels. In addition, it is shown that in order to have 100% capture efficiency for the GO sheets, a minimum solid content of the binary colloid is required, which can be identified experimentally as the minimum leading to gelation after passing through the MC only one time.

Sustainable endospore-based microreactor system for antioxidant capacity assay.

A novel endospore-based microbial method for "post-additional" antioxidant capacity assay was developed. The technique was based on oxidation and catalysis of the 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) by Bacillus subtilis 168 endospores in the presence of dissolved oxygen. Coat protein A (CotA), which belongs to the endospore coat, was expressed, purified, and assessed for its ability to oxidize ABTS into the ABTS(•+) radical cation. The wild-type endospore necessary for oxidizing ABTS into ABTS(•+) radical cation was confirmed by knocking out the cotA gene from B. subtilis 168 by homologous double exchange. Findings revealed that the catalytic activity of the endospores may be attributed to the presence of the CotA protein. The use of endospores instead of purified enzymes to prepare ABTS(•+) greatly reduced the assay cost and eliminated the need to purify and store of enzymes. The self-life of the radical cation was kept stable for at least 12 days without addition of a stabilizer and laccase inhibitor. This behavior enables the large-scale preparation of ABTS(•+). The antioxidant capacities of the individual antioxidants and fruit samples were easily quantified and compared using the proposed method. The developed technique can be further developed as a high-throughput screening technique for antioxidants.